tbuckley/cabot-search huggingface dataset:
Abstract P1106: Antiinflammatory Hydrogel Promotes Electrical Coupling After Myocardial Ischemia
Authors: Zhenhua Li
Journal: Circulation Research (2023)

Increased inflammation after myocardial ischemia contributes to abnormal cardiomyocyte electrical coupling, leading to inhomogeneities in ventricular conduction and retarded conduction velocity. It is highly desirable to selectively recruit the stem cells but block the inflammation. In this work, we reported a SDF-1α-encapsulated Puerarin (PUE) hydrogel (SDF-1α@PUE) that is capable of enhancing endogenous stem cell homing and simultaneously polarizing the recruited monocyte/macrophages into a repairing phenotype. These macrophages influenced the preservation of Cx43 protein content in heart which modulate intercellular coupling and improved cardiomyocyte electrical conduction. Furthermore, by taking advantage of the improved “soil”, the recruited stem cells mediated an improved cardiac function by preventing deterioration, promoting neovascular architecture, and reducing infarct size. Our findings demonstrated a promising therapeutic platform for MI which not only facilitates heart regeneration but also reduces the risk of cardiac arrhythmias.
Injectable Hydrogels Prepared Using Novel Synthetic Short Peptides with Defined Structure and Gelatin as Scaffolds to Support Cell and Tissue Growth
Authors: Ashlynn Ling Zhi Lee, Nithiyaa Balakrishnan, Jian Yao Ng, Shaoqiong Liu, Zhan Yuin Ong, Yanming Wang, Shujun Gao, Yi Yan Yang
Journal: Advanced Healthcare Materials (2023)

Animal-derived basement-membrane matrices such as Geltrex are used to grow cells and tissues. Particularly, these are commonly applied to support tumor growth in animals for cancer research. However, a material derived from an animal source has an undefined composition, and may thus have unavoidable batch-to-batch variation in properties. To overcome these issues, a series of synthetic short peptides to form hydrogels is designed in combination with gelatin to promote cell adhesion and growth. The peptides have sequences of (X1Y1X2Y2)
Engineered a dual-targeting HA-TPP/A nanoparticle for combination therapy against KRAS-TP53 co-mutation in gastrointestinal cancers
Authors: Yong Mei, Xiaohua Qin, Zhenyu Yang, Shiyao Song, Xiaoting Liu, Chong Wu, Jieying Qian, Xiaowan Huang, Yunjiao Zhang, Weiling He
Journal: Bioactive Materials (2023)

KRAS-TP53 co-mutation is strongly associated with poor prognosis and high malignancy in gastrointestinal cancers. Therefore, a novel approach to oncotherapy may lie in combination therapy targeting both KRAS and TP53. Herein, we present a novel self-assembled nanoparticle (HA-TPP/A) that are functionalized nano-carrier hyaluronic acid (HA)-TPP conjugate (HA-TPP) to degrade mutant p53 proteins (mutp53) and co-deliver AMG510 for treating KRAS-TP53 co-alteration of gastrointestinal cancers by inhibiting the mutant KRAS and mutp53 signaling pathways. The HA-TPP/A nanoparticles led to ubiquitination-dependent proteasomal degradation of mutp53 by targeting damage to mitochondria. Furthermore, these nanoparticles abrogated the gain-of-function (GOF) phenotypes of mutp53 and increased sensitivity to AMG510-induced cell killing, thereby reducing cell proliferation and migration in gastrointestinal cancer with KRAS-TP53 co-mutation. The co-loaded HA-TPP/A nanoparticles demonstrated remarkable therapeutic efficacy in a tumor-bearing mouse model, particularly in KRAS-TP53 double mutant expressing cancer cells, compared with single drug and combined free drug groups. Notably, HA-TPP/A is the first reported nanoparticle with an ability to co-target KRAS-TP53, providing a promising approach for therapy in highly malignant gastrointestinal tumors and potentially expanding clinical indications for AMG510 targeted therapies in gastrointestinal tumors.
Acute Kidney Injury With Empirical Antibiotics for Sepsis
Authors: Steven Y. C. Tong, Balasubramanian Venkatesh, Erin K. McCreary
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Physical activity and neurotrophic factors as potential drivers of neuroplasticity in Parkinson’s Disease: A systematic review and meta-analysis
Authors: Rossella Rotondo, Stefania Proietti, Marzia Perluigi, Elvira Padua, Fabrizio Stocchi, Massimo Fini, Vilberto Stocchi, Daniele Volpe, Maria Francesca De Pandis
Journal: Ageing Research Reviews (2023)
Residual circulating tumor DNA after adjuvant chemotherapy effectively predicts recurrence of stage II‐III gastric cancer
Authors: Shu‐Qiang Yuan, Run‐Cong Nie, You‐Sheng Huang, Ying‐Bo Chen, Si‐Yu Wang, Xiao‐Wei Sun, Yuan‐Fang Li, Ze‐Kun Liu, Yan‐Xing Chen, Yi‐Chen Yao, Yu Xu, Hai‐Bo Qiu, Yao Liang, Wei Wang, Ze‐Xian Liu, Qi Zhao, Rui‐Hua Xu, Zhi‐Wei Zhou, Feng Wang
Journal: Cancer Communications (2023)

Abstract Background Circulating tumor DNA (ctDNA) is a promising biomarker for predicting relapse in multiple solid cancers. However, the predictive value of ctDNA for disease recurrence remains indefinite in locoregional gastric cancer (GC). Here, we aimed to evaluate the predictive value of ctDNA in this context. Methods From 2016 to 2019, 100 patients with stage II/III resectable GC were recruited in this prospective cohort study (NCT02887612). Primary tumors were collected during surgical resection, and plasma samples were collected perioperatively and within 3 months after adjuvant chemotherapy (ACT). Somatic variants were captured via a targeted sequencing panel of 425 cancer‐related genes. The plasma was defined as ctDNA‐positive only if one or more variants detected in the plasma were presented in at least 2% of the primary tumors. Results Compared with ctDNA‐negative patients, patients with positive postoperative ctDNA had moderately higher risk of recurrence [hazard ratio (HR) = 2.74, 95% confidence interval (CI) = 1.37–5.48; P = 0.003], while patients with positive post‐ACT ctDNA showed remarkably higher risk (HR = 14.99, 95% CI = 3.08‐72.96; P &lt; 0.001). Multivariate analyses indicated that both postoperative and post‐ACT ctDNA positivity were independent predictors of recurrence‐free survival (RFS). Moreover, post‐ACT ctDNA achieved better predictive performance (sensitivity, 77.8%; specificity, 90.6%) than both postoperative ctDNA and serial cancer antigen. A comprehensive model incorporating ctDNA for recurrence risk prediction showed a higher C‐index (0.78; 95% CI = 0.71–0.84) than the model without ctDNA (0.71; 95% CI = 0.64–0.79; P = 0.009). Conclusions Residual ctDNA after ACT effectively predicts high recurrence risk in stage II/III GC, and the combination of tissue‐based and circulating tumor features could achieve better risk prediction.
The importance of residential dusk and dawn light exposure for sleep quality, health, and well-being
Authors: Femke Beute, Myriam BC. Aries
Journal: Sleep Medicine Reviews (2023)

Light exposure during twilight plays a critical role in the entrainment of the human circadian system. People are most often at home during dusk and dawn, and light exposure at home - either natural or from electric light - may therefore contribute substantially to sleep and well-being. However, very little research has focused on the effects of home lighting on sleep and well-being, and even less research has investigated the effects of light exposure during twilight. Therefore, a literature study was performed to collect studies on light exposure at home during dusk and dawn. Studies looking at light exposure during dusk and dawn have focused on either electric light intervention (i.e., dusk and dawn simulation) at home or in the laboratory or daylight exposure in the bedroom (i.e., the presence and type of curtains in the bedroom). Most research has focused on dawn simulation during the darker months of the year, often using sunrise alarms. In general, study results pointed to the importance of twilight light exposure at home for sleep and well-being. These results may depend on the characteristics of the user, such as age or chronotype.
Yellow Jack’s Potential Return to the American South
Authors: Peter J. Hotez, Angelle Desiree LaBeaud
Journal: New England Journal of Medicine (2023)

Interview with Peter Hotez on concerns that yellow fever could return to the southern United States. (08:37)Download Environmental and socioeconomic conditions in the U.S. South may permit sharp increases in the incidence of serious arbovirus infections, and yellow fever is of particular concern.
Current Medical Therapy for Adenomyosis: From Bench to Bedside
Authors: Andrea Etrusco, Fabio Barra, Vito Chiantera, Simone Ferrero, Stefano Bogliolo, Giulio Evangelisti, Engin Oral, Mariana Pastore, Alberto Izzotti, Renato Venezia, Marcello Ceccaroni, Antonio Simone Laganà
Journal: Drugs (2023)

Adenomyosis, characterized by the growth of endometrial tissue within the uterine wall, poses significant challenges in treatment. The literature primarily focuses on managing abnormal uterine bleeding (AUB) and dysmenorrhea, the main symptoms of adenomyosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) and tranexamic acid provide limited support for mild symptoms or symptom re-exacerbation during hormone therapy. The levonorgestrel-releasing intrauterine system (LNG-IUS) is commonly employed in adenomyosis management, showing promise in symptom improvement and reducing uterine size, despite the lack of standardized guidelines. Dienogest (DNG) also exhibits potential benefits, but limited evidence hinders treatment recommendations. Danazol, while effective, is limited by androgenic side effects. Combined oral contraceptives (COCs) may be less effective than progestins but can be considered for contraception in young patients. Gonadotropin-releasing hormone (GnRH) agonists effectively manage symptoms but induce menopausal symptoms with prolonged use. GnRH antagonists are a recent option requiring further investigation. Aromatase inhibitors (AIs) show promise in alleviating AUB and pelvic pain, but their safety necessitates exploration and limited use within trials for refractory patients. This review highlights the complexity of diagnosing adenomyosis, its coexistence with endometriosis and uterine leiomyomas, and its impact on fertility and quality of life, complicating treatment decisions. It emphasizes the need for research on guidelines for medical management, fertility outcomes, long-term effects of therapies, and exploration of new investigational targets. Future research should optimize therapeutic strategies, expand our understanding of adenomyosis and its management, and establish evidence-based guidelines to improve patient outcomes and quality of life.
Single-cell RNA sequencing of a new transgenic t(8;21) preleukemia mouse model reveals regulatory networks promoting leukemic transformation
Authors: Ming Yan, Mengdan Liu, Amanda G. Davis, Samuel A. Stoner, Dong-Er Zhang
Journal: Leukemia (2023)

Abstract T(8;21)(q22;q22), which generates the AML1-ETO fusion oncoprotein, is a common chromosomal abnormality in acute myeloid leukemia (AML) patients. Despite having favorable prognosis, 40% of patients will relapse, highlighting the need for innovative models and application of the newest technologies to study t(8;21) leukemogenesis. Currently, available AML1-ETO mouse models have limited utility for studying the pre-leukemic stage because AML1-ETO produces mild hematopoietic phenotypes and no leukemic transformation. Conversely, overexpression of a truncated variant, AML1-ETO9a (AE9a), promotes fully penetrant leukemia and is too potent for studying pre-leukemic changes. To overcome these limitations, we devised a germline-transmitted Rosa26 locus AE9a knock-in mouse model that moderately overexpressed AE9a and developed leukemia with long latency and low penetrance. We observed pre-leukemic alterations in AE9a mice, including skewing of progenitors towards granulocyte/monocyte lineages and replating of stem and progenitor cells. Next, we performed single-cell RNA sequencing to identify specific cell populations that contribute to these pre-leukemic phenotypes. We discovered a subset of common myeloid progenitors that have heightened granulocyte/monocyte bias in AE9a mice. We also observed dysregulation of key hematopoietic transcription factor target gene networks, blocking cellular differentiation. Finally, we identified Sox4 activation as a potential contributor to stem cell self-renewal during the pre-leukemic stage.
Targeted hyperalkalization with NaOH-loaded starch implants enhances doxorubicin efficacy in tumor treatment
Authors: Changkyu Lee
Journal: Asian Journal of Pharmaceutical Sciences (2023)

High-alkali treatment using sodium hydroxide (NaOH) injection can be a therapeutic approach for killing tumor cells. Alkalization can damage cellular structures and lead to cell death. Increased alkalinity can also enhance the efficacy of certain chemotherapeutic drugs such as doxorubicin (DOX). In this study, NaOH-loaded starch implants (NST implants) were used to induce hyperalkalization (increase pH) in the tumor environment, thereby inducing necrosis and enhancing the effects of DOX. NaOH is a strongly alkaline substance that can increase the pH when injected into a tumor. However, the administration of NaOH can have toxic side effects because it increases the pH of the entire body, not just at the tumor site. To overcome this problem, we developed an injectable NST implant, in which NaOH can be delivered directly into the tumor. This study showed that NST implants could be easily administered intratumorally in mice bearing 4T1 tumors and that most of the NaOH released from the NST implants was delivered to the tumors. Although some NaOH from NST implants can be systemically absorbed, it is neutralized by the body's buffering effect, thereby reducing the risk of toxicity. This study also confirmed both in vitro and in vivo that DOX is more effective at killing 4T1 cells when alkalized. It has been shown that administration of DOX after injection of an NST implant can kill most tumors. Systemic absorption and side effects can be reduced using an NST implant to deliver NaOH to the tumor. In addition, alkalinization induced by NST implants not only exerts anticancer effects but can also enhance the effect of DOX in killing cancer cells. Therefore, the combination of NaOH-loaded starch implants and DOX treatment has the potential to be a novel therapy for tumors.
FUNDC1/PFKP-mediated mitophagy induced by KD025 ameliorates cartilage degeneration in osteoarthritis
Authors: Guibin Fang, Xingzhao Wen, Zongrui Jiang, Xue Du, Ruonan Liu, Chengyun Zhang, Guiwu Huang, Weiming Liao, Zhiqi Zhang
Journal: Molecular Therapy (2023)
Clinical effectiveness of point of care tests for diagnosing urinary tract infection: a systematic review
Authors: Eve Tomlinson, Hayley E. Jones, Rachel James, Chris Cooper, Christina Stokes, Samina Begum, Jessica Watson, Alastair D. Hay, Mary Ward, Howard Thom, Penny Whiting
Journal: Clinical Microbiology and Infection (2023)

Point of care tests (POCTs) have the potential to improve the urinary tract infection (UTI) diagnostic pathway, as they can provide a diagnosis quickly in near-patient settings, and some also identify causative pathogens/antimicrobial sensitivity.
Phase 2 open-label, multicenter, single-arm study of cemiplimab in patients with locally advanced basal cell carcinoma after hedgehog inhibitor therapy: Extended follow-up
Authors: Alexander J. Stratigos, Aleksandar Sekulic, Ketty Peris, Oliver Bechter, Sorilla Prey, Karl D. Lewis, Nicole Basset-Seguin, Anne Lynn S. Chang, Stéphane Dalle, Almudena Fernández Orland, Lisa Licitra, Caroline Robert, Claas Ulrich, Axel Hauschild, Michael R. Migden, Reinhard Dummer, Suk-Young Yoo, Emmanuel Okoye, Ioannis Bassukas, Carmen Loquai, Vincenzo De Giorgi, Zeynep Eroglu, Ralf Gutzmer, Jens Ulrich, Susana Puig, Timothy J. Inocencio, Chieh-I Chen, Patrick R. LaFontaine, Frank Seebach, Israel Lowy, Matthew G. Fury
Journal: Journal of the American Academy of Dermatology (2023)
Multiple infusions of ex vivo-expanded regulatory T cells promote CD163+ myeloid cells and kidney allograft survival in non-lymphodepleted non-human primates
Authors: Kazuki Sasaki, Masahiko Kubo, Yu-chao Wang, Lien Lu, Veronica Vujevich, Michelle A. Wood-Trageser, Kayla Golnoski, Andrew Lesniak, Vikraman Gunabushanam, Armando Ganoza, Martin J. Wijkstrom, Abhinav Humar, Anthony J. Demetris, Angus W. Thomson, Mohamed B. Ezzelarab
Journal: Kidney International (2023)
Improved homogeneity and monotonicity of American Joint Committee on Cancer staging manual, 8th edition on cutaneous squamous cell carcinoma with addition of poor differentiation
Authors: Neha Gupta, Patrick M. Mulvaney, Fadi Murad, Brian R. Gastman, Evelyn Ilori, Shlomo Koyfman, Chrysalyne D. Schmults, Allison T. Vidimos, Emily S. Ruiz
Journal: Journal of the American Academy of Dermatology (2023)
Idasanutlin and navitoclax induce synergistic apoptotic cell death in T-cell acute lymphoblastic leukemia
Authors: Kimberly B. Johansson, Megan S. Zimmerman, Iryna V. Dmytrenko, Feng Gao, Daniel C. Link
Journal: Leukemia (2023)

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy in which activating mutations in the Notch pathway are thought to contribute to transformation, in part, by activating c-Myc. Increased c-Myc expression induces oncogenic stress that can trigger apoptosis through the MDM2-p53 tumor suppressor pathway. Since the great majority of T-ALL cases carry inactivating mutations upstream in this pathway but maintain wildtype MDM2 and TP53 , we hypothesized that T-ALL would be selectively sensitive to MDM2 inhibition. Treatment with idasanutlin, an MDM2 inhibitor, induced only modest apoptosis in T-ALL cells but upregulated the pro-apoptotic BH3 domain genes BAX and BBC3 , prompting us to evaluate the combination of idasanutlin with BH3 mimetics. Combination treatment with idasanutlin and navitoclax, a potent Bcl-2/Bcl-xL inhibitor, induces more consistent and potent synergistic killing of T-ALL PDX lines in vitro than venetoclax, a Bcl-2 specific inhibitor. Moreover, a marked synergic response to combination treatment with idasanutlin and navitoclax was seen in vivo in all four T-ALL xenografts tested, with a significant increase in overall survival in the combination treatment group. Collectively, these preclinical data show that the combination of idasanutlin and navitoclax is highly active in T-ALL and may merit consideration in the clinical setting.
Humoral immune response characteristics of the elderly, children and pregnant women after XBB infection
Authors: Fen Ouyang, Huan Zhang, Yushan Jiang, Hesong Wang, Tingting Peng,, Chang Xi, Jianhai Yu, Zhuolin Li, Jiayin Chen, Linfan Wu, Bao Zhang, Wei Zhao, Baisheng Li, Shi Ouyang, Chenguang Shen
Journal: Journal of Infection (2023)
Use of omalizumab is associated with improvement of pruritic skin disorders induced by immune checkpoint inhibitors: A retrospective cohort from the European Task Force of Dermatology for Cancer patients
Authors: Francesc Alamon-Reig, Xavier Bosch-Amate, Priscila Giavedoni, Vasiliki Nikolaou, Cristina Mangas, Zoe Apalla, Ander Mayor, Chrysa Oikonomou, Michela Starace, Vincent Sibaud, Cristina Carrera
Journal: Journal of the American Academy of Dermatology (2023)
Silica nanoparticles: A review of their safety and current strategies to overcome biological barriers
Authors: Taskeen Iqbal Janjua, Yuxue Cao, Freddy Kleitz, Mika Linden, Chengzhong Yu, Amirali Popat
Journal: Advanced Drug Delivery Reviews (2023)

Silica nanoparticles (SNP) have gained tremendous attention in the recent decades. They have been used in many different biomedical fields including diagnosis, biosensing and drug delivery. Medical uses of SNP for anti-cancer, anti-microbial and theranostic applications are especially prominent due to their exceptional performance to deliver many different small molecules and recently biologics (mRNA, siRNA, antigens, antibodies, proteins, and peptides) at targeted sites. The physical and chemical properties of SNP such as large specific surface area, tuneable particle size and porosity, excellent biodegradability and biocompatibility make them an ideal drug delivery and diagnostic platform. Based on the available data and the pre-clinical performance of SNP, recent interest has driven these innovative materials towards clinical application with many of the formulations already in Phase I and Phase II trials. Herein, the progress of SNP in biomedical field is reviewed, and their safety aspects are analysed. Importantly, we critically evaluate the key structural characteristics of SNP to overcome different biological barriers including the blood-brain barrier (BBB), skin, tumour barrier and mucosal barrier. Future directions, potential pathways, and target areas towards rapid clinical translation of SNP are also recommended.
A trillion trees: carbon capture or fuelling fires?
Authors: Nicola Stevens, William J. Bond
Journal: Trends in Ecology & Evolution (2023)

Afforesting grassy systems for carbon gain using flammable plantation trees could shift the fire regime from lower intensity grass-fuelled fires to high-intensity crown fires. Future changes in climate will worsen this. We highlight the fire risk of trees planted for carbon and costs of fire protection using African examples.